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Cannabidiol Bioavailability Trial With Oral Multiple Dose Administration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04790136
Recruitment Status : Completed
First Posted : March 10, 2021
Last Update Posted : July 13, 2021
Sponsor:
Collaborators:
Glatt Pharmaceutical Services GmbH & Co. KG
SocraMetrics GmbH
Information provided by (Responsible Party):
SocraTec R&D GmbH

Brief Summary:

Glatt Pharmaceutical Services GmbH & Co. KG is developing a new CBD granules formulation (GLA-015 / Cannabidiol 1500 mg 29,7% w/w GRA BLD P) which is intended to be used in the treatment of the new Coronavirus disease 2019 (COVID-19). Due to its enhanced solubility the new product is expected to show increased bioavailability, reduced variability especially in the fasted state and better robustness towards food interaction compared to oil-based cannabidiol solutions.

The aim of the present clinical trial is the characterisation of maximum systemic exposure of CBD and its active metabolite 7-OH-CBD of the newly developed Test product in the estimated target effective dose for treatment of COVID-19 as well as the comparison of its systemic bioavailability to CBD administered as oily solution.

Comparison of maximum systemic exposure of Test vs. Reference will be performed under steady state conditions with twice daily intake after a light meal over 7 consecutive days.


Condition or disease Intervention/treatment Phase
Comparative Bioavailability Drug: GLA-015 Drug: DAC C-052 "Cannabidiol" / NRF 22.10 "Oily cannabidiol solution 100 mg/ml" Phase 1

Detailed Description:

This single centre, open-label, randomised (order of treatments), balanced, multiple dose trial will be performed in a 2-period, 2-sequence-crossover design with direct switch-over. Eighteen (18) healthy subjects of both sexes (balanced distribution intended, but minimum 40% of each sex) are intended to be randomised.

The IMPs will be administered after a light meal as single oral doses of 1500 mg cannabidiol (i.e. 5.051 g granules of Test to be dispersed in water or 15 ml solution of Reference) twice daily (i.e. every 12 h) over 7 consecutive days.

Blood sampling will be performed after the 13th administration over 24 h, thereby including the 14th administration, in order to characterise pharmacokinetic parameters after multiple dosing over a whole day interval.

Comparison of maximum systemic exposure of Test vs. Reference will be performed under steady state conditions by means of AUC144-168,ss, Cmax,144-168,ss, and Cmin,144-168,ss of CBD and 7-OH-CBD.

The clinical trial will be performed as a cross-over investigation with intra-individual comparison, thus reducing variability of the pharmacokinetic parameters, which is supposed to be higher between subjects than within an individual subject.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Characterisation of Relative Bioavailability of GLA-015 in Comparison With an Oily Cannabidiol Solution (NRF 22.10) - a Multiple Dose, Randomised, 2-period Crossover-trial With Twice Daily Administration in Healthy Adult Male and Female Subjects
Actual Study Start Date : March 17, 2021
Actual Primary Completion Date : April 16, 2021
Actual Study Completion Date : May 12, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Cannabidiol

Arm Intervention/treatment
Experimental: GLA-015
GLA-015 (Glatt Pharmaceutical Services GmbH & Co. KG, Germany); 5.051 g granules containing 1500 mg cannabidiol to be dispersed in water; oral multiple dose administration twice daily over 7 consecutive days after a light meal
Drug: GLA-015
administration followed by PK blood sampling

Active Comparator: DAC C-052 "Cannabidiol" / NRF 22.10 "Oily cannabidiol solution 100 mg/ml"
DAC C-052 "Cannabidiol" / NRF 22.10 "Ölige Cannabidiol-Lösung 100 mg/ml" ("Oily cannabidiol solution 100 mg/ml") (Glatt Pharmaceutical Services GmbH & Co. KG, Germany; according to DAC/NRF specifications); 15 ml solution containing 1500 mg cannabidiol; oral multiple dose administration twice daily over 7 consecutive days after a light meal
Drug: DAC C-052 "Cannabidiol" / NRF 22.10 "Oily cannabidiol solution 100 mg/ml"
administration followed by PK blood sampling




Primary Outcome Measures :
  1. Comparison of relative bioavailability of Test vs. Reference after multiple dose administration after a light meal determined by use of AUC144-168,ss of cannabidiol [ Time Frame: 24 hours ]
    AUC144-168,ss = partial area under the concentration vs. time curve over both dosing intervals on PK profiling day (i.e. starting with the morning dose on study day 7 to 12 h after the evening dose on study day 7), calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations)

  2. Comparison of relative bioavailability of Test vs. Reference after multiple dose administration after a light meal determined by use of Cmax,144-168,ss of cannabidiol [ Time Frame: 24 hours ]
    Cmax,144-168,ss = observed maximum concentration over both dosing intervals on PK profiling day (i.e. starting with the morning dose on study day 7 to 12 h after the evening dose on study day 7), considering scheduled times

  3. Comparison of relative bioavailability of Test vs. Reference after multiple dose administration after a light meal determined by use of Cmin,144-168,ss of cannabidiol [ Time Frame: 24 hours ]
    Cmin,144-168,ss = (absolute) minimum concentrations over both dosing intervals on PK profiling day (i.e. starting with the morning dose on study day 7 to 12 h after the evening dose on study day 7), considering scheduled times

  4. Comparison of relative bioavailability of Test vs. Reference after multiple dose administration after a light meal determined by use of AUC144-168,ss of 7-OH-CBD [ Time Frame: 24 hours ]
    AUC144-168,ss = partial area under the concentration vs. time curve over both dosing intervals on PK profiling day (i.e. starting with the morning dose on study day 7 to 12 h after the evening dose on study day 7), calculated by means of the linear up/log down method (linear trapezoidal rule for increases in concentration/logarithmic trapezoidal rule for decreases in concentrations)

  5. Comparison of relative bioavailability of Test vs. Reference after multiple dose administration after a light meal determined by use of Cmax,144-168,ss, of 7-OH-CBD [ Time Frame: 24 hours ]
    Cmax,144-168,ss = observed maximum concentration over both dosing intervals on PK profiling day (i.e. starting with the morning dose on study day 7 to 12 h after the evening dose on study day 7), considering scheduled times

  6. Comparison of relative bioavailability of Test vs. Reference after multiple dose administration after a light meal determined by use of Cmin,144-168,ss of 7-OH-CBD [ Time Frame: 24 hours ]
    Cmin,144-168,ss = (absolute) minimum concentrations over both dosing intervals on PK profiling day (i.e. starting with the morning dose on study day 7 to 12 h after the evening dose on study day 7), considering scheduled times


Secondary Outcome Measures :
  1. Frequency of Adverse Events [ Time Frame: 14 days ]
    Descriptive statistics with regard to frequency of adverse events considering intensity, relationship to the IMP, action taken, outcome, and seriousness as well as period and treatment

  2. Frequency of subjects showing Adverse Events [ Time Frame: 14 days ]
    Descriptive statistics with regard to frequency of subjects showing adverse events considering intensity, relationship to the IMP, action taken, outcome, and seriousness as well as period and treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. ethnic origin: Caucasian
  2. age: 18 years or older (including)
  3. body-mass index (BMI): >= 18.5 kg/m² and <= 30.0 kg/m²
  4. good state of health
  5. non-smoker or ex-smoker for at least 1 month
  6. written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial

Exclusion Criteria:

Safety concerns

  1. existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
  2. existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient
  3. existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient
  4. history of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
  5. hepatic impairment
  6. history of bradycardia, tachycardia or other arrhythmic symptoms of clinical significance
  7. Nurses Global Assessment of Suicide Risk (NGASR)-scale showing a high or very high risk
  8. known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations
  9. history of severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
  10. systolic blood pressure < 90 or > 139 mmHg
  11. diastolic blood pressure < 60 or > 89 mmHg
  12. heart rate < 50 bpm or > 90 bpm
  13. QTc interval > 450 ms for men and > 470 ms for women
  14. ASAT > 20% ULN, ALAT > 10% ULN, bilirubin > 20% ULN (except in case of existing Morbus Gilbert-Meulengracht deduced from anamnesis/medical history) and creatinine > 0.1 mg/dL ULN (limit of > 0.1 mg/dL correspondents to of > 9 µmol/l ULN)
  15. all other laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator
  16. positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test or anti-HCV-test
  17. diagnosis of COVID-19 within the last 14 days prior to individual enrolment of the subject
  18. contact to persons in foreign risk regions as defined by the Robert Koch Institute within the last 14 days prior to individual enrolment of the subject
  19. known direct contact with insufficient protection to persons with diagnosis of COVID-19 within the last 14 days prior to individual enrolment upon reporting of the subject

    Lack of suitability for the clinical trial

  20. acute or chronic diseases which may interfere with the pharmacokinetics of the IMP
  21. history of or current drug or alcohol dependence
  22. positive alcohol, cotinine or drug test at screening examination
  23. regular intake of alcoholic food or beverages of ≥ 24 g pure ethanol for male or ≥ 12 g pure ethanol for female per day
  24. subjects who are on a diet which could affect the pharmacokinetics of the active ingredient
  25. regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day
  26. blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject
  27. administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject
  28. regular treatment with any systemically available medication (except hormonal contraceptives and hormonal replacement therapy, e.g. estrogens, L-thyroxine)
  29. subjects, who report a frequent occurrence of migraine attacks

    For female subjects with childbearing potential only:

  30. positive pregnancy test at screening examination
  31. pregnant or lactating women
  32. female subjects who do not agree to apply highly effective contraceptive methods

    Administrative reasons

  33. subjects suspected or known not to follow instructions
  34. subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04790136


Locations
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Germany
SocraTec R&D GmbH Clinical Pharmacology Unit
Erfurt, Thuringia, Germany, 99084
Sponsors and Collaborators
SocraTec R&D GmbH
Glatt Pharmaceutical Services GmbH & Co. KG
SocraMetrics GmbH
Investigators
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Principal Investigator: Frank Donath SocraTec R&D GmbH Clinical Pharmacology Unit
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Responsible Party: SocraTec R&D GmbH
ClinicalTrials.gov Identifier: NCT04790136    
Other Study ID Numbers: 1393cbd20ct
2020-004807-15 ( EudraCT Number )
First Posted: March 10, 2021    Key Record Dates
Last Update Posted: July 13, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SocraTec R&D GmbH:
Bioavailability
Cannabidiol
Additional relevant MeSH terms:
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Cannabidiol
Anticonvulsants